tbuckley/cabot-search huggingface dataset:
Lipocalin‐2 activates hepatic stellate cells and promotes nonalcoholic steatohepatitis in high‐fat diet–fed Ob/Ob mice
Authors: Kyung Eun Kim, Jaewoong Lee, Hyun Joo Shin, Eun Ae Jeong, Hye Min Jang, Yu Jeong Ahn, Hyeong Seok An, Jong Youl Lee, Meong Cheol Shin, Soo Kyoung Kim, Won Gi Yoo, Won Ho Kim, Gu Seob Roh
Journal: Hepatology (2022)

Background and Aims: In obesity and type 2 diabetes mellitus, leptin promotes insulin resistance and contributes to the progression of NASH via activation of hepatic stellate cells (HSCs). However, the pathogenic mechanisms that trigger HSC activation in leptin‐deficient obesity are still unknown. This study aimed to determine how HSC‐targeting lipocalin‐2 (LCN2) mediates the transition from simple steatosis to NASH. Approach and Results: Male wild‐type (WT) and ob/ob mice were fed a high‐fat diet (HFD) for 20 weeks to establish an animal model of NASH with fibrosis. Ob/ob mice were subject to caloric restriction or recombinant leptin treatment. Double knockout (DKO) mice lacking both leptin and lcn2 were also fed an HFD for 20 weeks. In addition, HFD‐fed ob/ob mice were treated with gadolinium trichloride to deplete Kupffer cells. The LX‐2 human HSCs and primary HSCs from ob/ob mice were used to investigate the effects of LCN2 on HSC activation. Serum and hepatic LCN2 expression levels were prominently increased in HFD‐fed ob/ob mice compared with normal diet‐fed ob/ob mice or HFD‐fed WT mice, and these changes were closely linked to liver fibrosis and increased hepatic α‐SMA/matrix metalloproteinase 9 (MMP9)/signal transducer and activator of transcription 3 (STAT3) protein levels. HFD‐fed DKO mice showed a marked reduction of α‐SMA protein compared with HFD‐fed ob/ob mice. In particular, the colocalization of LCN2 and α‐SMA was increased in HSCs from HFD‐fed ob/ob mice. In primary HSCs from ob/ob mice, exogenous LCN2 treatment induced HSC activation and MMP9 secretion. By contrast, LCN2 receptor 24p3R deficiency or a STAT3 inhibitor reduced the activation and migration of primary HSCs. Conclusions: LCN2 acts as a key mediator of HSC activation in leptin‐deficient obesity via α‐SMA/MMP9/STAT3 signaling, thereby exacerbating NASH.
SARS-CoV-2 mRNA Vaccine Antibody Response in Patients with Asthma Receiving Biologic Therapy: A Real-World Analysis
Authors: Shu-Yi Liao, Anthony N. Gerber, Pearlanne Zelarney, Barry Make, Michael E. Wechsler
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"SARS-CoV-2 mRNA Vaccine Antibody Response in Asthma Patients with Biologic Therapy after Second and Booster Dose: A Real-world Analysis." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline
Authors: Jennifer A. Ligibel, Kari Bohlke, Anne M. May, Steven K. Clinton, Wendy Demark-Wahnefried, Susan C. Gilchrist, Melinda L. Irwin, Michele Late, Sami Mansfield, Timothy F. Marshall, Jeffrey A. Meyerhardt, Cynthia A. Thomson, William A. Wood, Catherine M. Alfano
Journal: Journal of Clinical Oncology (2022)

To provide guidance on exercise, diet, and weight management during active cancer treatment in adults.A systematic review of the literature identified systematic reviews and randomized controlled trials evaluating the impact of aerobic and resistance exercise, specific diets and foods, and intentional weight loss and avoidance of weight gain in adults during cancer treatment, on quality of life, treatment toxicity, and cancer control. PubMed and the Cochrane Library were searched from January 2000 to May 2021. ASCO convened an Expert Panel to review the evidence and formulate recommendations.The evidence base consisted of 52 systematic reviews (42 for exercise, nine for diet, and one for weight management), and an additional 23 randomized controlled trials. The most commonly studied types of cancer were breast, prostate, lung, and colorectal. Exercise during cancer treatment led to improvements in cardiorespiratory fitness, strength, fatigue, and other patient-reported outcomes. Preoperative exercise in patients with lung cancer led to a reduction in postoperative length of hospital stay and complications. Neutropenic diets did not decrease risk of infection during cancer treatment.Oncology providers should recommend regular aerobic and resistance exercise during active treatment with curative intent and may recommend preoperative exercise for patients undergoing surgery for lung cancer. Neutropenic diets are not recommended to prevent infection in patients with cancer during active treatment. Evidence for other dietary and weight loss interventions during cancer treatment was very limited. The guideline discusses special considerations, such as exercise in individuals with advanced cancer, and highlights the critical need for more research in this area, particularly regarding diet and weight loss interventions during cancer treatment.Additional information is available at www.asco.org/supportive-care-guidelines.
Screening for Chronic Obstructive Pulmonary Disease
Authors: Surya P. Bhatt, George T. O’Connor
Journal: JAMA (2022)

US Preventive Services Task Force; Carol M. Mangione, MD, MSPH; Michael J. Barry, MD; Wanda K. Nicholson, MD, MPH, MBA; Michael Cabana, MD, MA, MPH; Aaron B. Caughey, MD, MPH; David Chelmow, MD; Tumaini Rucker Coker, MD, MBA; Esa M. Davis, MD, MPH; Katrina E. Donahue, MD, MPH; Carlos Roberto Jaén, MD, PhD, MS; Martha Kubik, PhD, RN; Li Li, MD, PhD, MPH; Gbenga Ogedegbe, MD, MPH; Lori Pbert, PhD; John M. Ruiz, PhD; James Stevermer, MD, MSPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD
Efficacy of a computer-aided detection system in a fecal immunochemical test-based organized colorectal cancer screening program: a randomized controlled trial (AIFIT study)
Authors: Emanuele Rondonotti, Dhanai Di Paolo, Erik Rosa Rizzotto, Costanza Alvisi, Elisabetta Buscarini, Marco Spadaccini, Giacomo Tamanini, Silvia Paggi, Arnaldo Amato, Giulia Scardino, Samanta Romeo, Saverio Alicante, Fabio Ancona, Ennio Guido, Vincenza Marzo, Fabio Chicco, Simona Agazzi, Cesare Rosa, Loredana Correale, Alessandro Repici, Cesare Hassan, Franco Radaelli
Journal: Endoscopy (2022)

Abstract Background Computer-aided detection (CADe) increases adenoma detection in primary screening colonoscopy. The potential benefit of CADe in a fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening program is unknown. This study assessed whether use of CADe increases the adenoma detection rate (ADR) in a FIT-based CRC screening program. Methods In a multicenter, randomized trial, FIT-positive individuals aged 50–74 years undergoing colonoscopy, were randomized (1:1) to receive high definition white-light (HDWL) colonoscopy, with or without a real-time deep-learning CADe by endoscopists with baseline ADR &gt; 25 %. The primary outcome was ADR. Secondary outcomes were mean number of adenomas per colonoscopy (APC) and advanced adenoma detection rate (advanced-ADR). Subgroup analysis according to baseline endoscopists’ ADR (≤ 40 %, 41 %–45 %, ≥ 46 %) was also performed. Results 800 individuals (median age 61.0 years [interquartile range 55–67]; 409 men) were included: 405 underwent CADe-assisted colonoscopy and 395 underwent HDWL colonoscopy alone. ADR and APC were significantly higher in the CADe group than in the HDWL arm: ADR 53.6 % (95 %CI 48.6 %–58.5 %) vs. 45.3 % (95 %CI 40.3 %–50.45 %; RR 1.18; 95 %CI 1.03–1.36); APC 1.13 (SD 1.54) vs. 0.90 (SD 1.32; P = 0.03). No significant difference in advanced-ADR was found (18.5 % [95 %CI 14.8 %–22.6 %] vs. 15.9 % [95 %CI 12.5 %–19.9 %], respectively). An increase in ADR was observed in all endoscopist groups regardless of baseline ADR. Conclusions Incorporating CADe significantly increased ADR and APC in the framework of a FIT-based CRC screening program. The impact of CADe appeared to be consistent regardless of endoscopist baseline ADR.
Interferon regulatory factor 1 (IRF1) controls the metabolic programmes of low-grade pancreatic cancer cells
Authors: Gabriele Alfarano, Matteo Audano, Pierluigi Di Chiaro, Chiara Balestrieri, Marta Milan, Sara Polletti, Paola Spaggiari, Alessandro Zerbi, Giuseppe Riccardo Diaferia, Nico Mitro, Gioacchino Natoli
Journal: Gut (2022)

Pancreatic ductal adenocarcinomas (PDACs) include heterogeneous mixtures of low-grade cells forming pseudoglandular structures and compact nests of high-grade cells organised in non-glandular patterns. We previously reported that low-grade PDAC cells display high expression of interferon regulatory factor 1 (IRF1), a pivotal transcription factor of the interferon (IFN) system, suggesting grade-specific, cell-intrinsic activation of IFN responses. Here, we set out to determine the molecular bases and the functional impact of the activation of IFN-regulated responses in human PDACs.We first confirmed the correlation between glandular differentiation and molecular subtypes of PDAC on the one hand, and the expression of IRF1 and IFN-stimulated genes on the other. We next used unbiased omics approaches to systematically analyse basal and IFN-regulated responses in low-grade and high-grade PDAC cells, as well as the impact of IRF1 on gene expression programmes and metabolic profiles of PDAC cells.High-level expression of IRF1 in low-grade PDAC cells was controlled by endodermal lineage-determining transcription factors. IRF1-regulated gene expression equipped low-grade PDAC cells with distinctive properties related to antigen presentation and processing as well as responsiveness to IFN stimulation. Notably, IRF1 also controlled the characteristic metabolic profile of low-grade PDAC cells, suppressing both mitochondrial respiration and fatty acid synthesis, which may in part explain its growth-inhibiting activity.IRF1 links endodermal differentiation to the expression of genes controlling antigen presentation and processing as well as to the specification of the metabolic profile characteristic of classical PDAC cells.
Bone Uptake in Prostate Cancer Patients
Authors: Anouk Letang, Amandine Crombé, Caroline Rousseau, Paul Sargos, Charles Merlin, Coralie Cantarel, Anne-Laure Cazeau
Journal: Clinical Nuclear Medicine (2022)

Purpose 68 Gallium-labeled prostate-specific membrane antigen-11 (PSMA) PET/CT is the new reference to identify relapse during biochemical recurrence of prostate cancer (PCa). However, this method lacks specificity for bone foci. This study aimed to report the prevalence of PCa bone metastases and to assess the diagnostic performances of PSMA reporting and data systems (RADS), clinical, biological, and imaging features for identification. Patients and Methods A multicentric retrospective cohort of consecutive patients with biochemical recurrence after local treatment was analyzed. Clinical and biological features at initial staging and during recurrence were retrieved from medical reports. The metastatic status of each bone uptake on PSMA PET/CT was determined according to histopathology, comparisons with concomitant and previous conventional imaging, prostate-specific antigen kinetic, and follow-up. Two nuclear medicine physicians assessed PSMA-RADS, anatomic location, radiological patterns, SUV max , and the presence of other molecular lesions. Univariate and multivariate analyses were conducted to identify independent predictors of PCa metastases. Results In the eligible population, 98/298 patients (32.9%) showed bone uptake on PSMA PET/CT. In patients with a final diagnosis, 28/81 lesions (34.6%) were metastases. PSMA-RADS-4 or 5 showed sensitivity of 79%, specificity of 94%, and accuracy of 89%. PSMA-RADS had a significantly higher area under the receiver operating characteristic curve than the initial reading in clinical practice (0.91 vs 0.83, P = 0.0074). Initial Gleason score ≥8, age ≤71 years at recurrence, and SUV max &gt;6.21 were independent predictors of PCa metastases in multivariate logistic regression ( P = 0.0314, 0.0179, and 0.0003, respectively). Conclusions Most bone uptakes at PSMA PET/CT were benign lesions. PSMA-RADS, patients and tumor characteristics, and SUV max could help identify PCa bone metastases.
Comment on Aminian et al. Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity: Comparison of Gastric Bypass, Sleeve Gastrectomy, and Usual Care. Diabetes Care 2021;44:2552–2563
Authors: Jorge Rafael Violante-Cumpa, Raymundo Abram Sánchez-Gómez, Fernando Javier Lavalle-González, Leonardo Guadalupe Mancillas-Adame
Journal: Diabetes Care (2022)
Mycoplasma pneumoniae detections before and during the COVID-19 pandemic: results of a global survey, 2017 to 2021
Authors: Patrick M Meyer Sauteur, Michael L Beeton, Søren A Uldum, Nathalie Bossuyt, Melissa Vermeulen, Katherine Loens, Sabine Pereyre, Cécile Bébéar, Darja Keše, Jessica Day, Baharak Afshar, Victoria J Chalker, Gilbert Greub, Ran Nir-Paz, Roger Dumke
Journal: Eurosurveillance (2022)

BackgroundMycoplasma pneumoniae respiratory infections are transmitted by aerosol and droplets in close contact.AimWe investigated global M. pneumoniae incidence after implementation of non-pharmaceutical interventions (NPIs) against COVID-19 in March 2020.MethodsWe surveyed M. pneumoniae detections from laboratories and surveillance systems (national or regional) across the world from 1 April 2020 to 31 March 2021 and compared them with cases from corresponding months between 2017 and 2020. Macrolide-resistant M. pneumoniae (MRMp) data were collected from 1 April 2017 to 31 March 2021.ResultsThirty-seven sites from 21 countries in Europe, Asia, America and Oceania submitted valid datasets (631,104 tests). Among the 30,617 M. pneumoniae detections, 62.39% were based on direct test methods (predominantly PCR), 34.24% on a combination of PCR and serology (no distinction between methods) and 3.37% on serology alone (only IgM considered). In all countries, M. pneumoniae incidence by direct test methods declined significantly after implementation of NPIs with a mean of 1.69% (SD ± 3.30) compared with 8.61% (SD ± 10.62) in previous years (p < 0.01). Detection rates decreased with direct but not with indirect test methods (serology) (-93.51% vs + 18.08%; p < 0.01). Direct detections remained low worldwide throughout April 2020 to March 2021 despite widely differing lockdown or school closure periods. Seven sites (Europe, Asia and America) reported MRMp detections in one of 22 investigated cases in April 2020 to March 2021 and 176 of 762 (23.10%) in previous years (p = 0.04).ConclusionsThis comprehensive collection of M. pneumoniae detections worldwide shows correlation between COVID-19 NPIs and significantly reduced detection numbers.
Telaglenastat plus Everolimus in Advanced Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled, Phase II ENTRATA Trial
Authors: Chung-Han Lee, Robert Motzer, Hamid Emamekhoo, Marc Matrana, Ivor Percent, James J. Hsieh, Arif Hussain, Ulka Vaishampayan, Sandy Liu, Steven McCune, Vijay Patel, Montaser Shaheen, Johanna Bendell, Alice C. Fan, Benjamin A. Gartrell, Oscar B. Goodman, Petros G. Nikolinakos, Arash Rezazadeh Kalebasty, Yousef Zakharia, Zhentao Zhang, Hema Parmar, Lalith Akella, Keith Orford, Nizar M. Tannir
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Glutaminase is a key enzyme, which supports elevated dependency of tumors on glutamine-dependent biosynthesis of metabolic intermediates. Dual targeting of glucose and glutamine metabolism by the mTOR inhibitor everolimus plus the oral glutaminase inhibitor telaglenastat showed preclinical synergistic anticancer effects, which translated to encouraging safety and efficacy findings in a phase I trial of 2L+ renal cell carcinoma (RCC). This study evaluated telaglenastat plus everolimus (TelaE) versus placebo plus everolimus (PboE) in patients with advanced/metastatic RCC (mRCC) in the 3L+ setting (NCT03163667). Patients and Methods: Eligible patients with mRCC, previously treated with at least two prior lines of therapy [including ≥1 VEGFR-targeted tyrosine kinase inhibitor (TKI)] were randomized 2:1 to receive E, plus Tela or Pbo, until disease progression or unacceptable toxicity. Primary endpoint was investigator-assessed progression-free survival (PFS; one-sided α &amp;lt;0.2). Results: Sixty-nine patients were randomized (46 TelaE, 23 PboE). Patients had a median three prior lines of therapy, including TKIs (100%) and checkpoint inhibitors (88%). At median follow-up of 7.5 months, median PFS was 3.8 months for TelaE versus 1.9 months for PboE [HR, 0.64; 95% confidence interval (CI), 0.34–1.20; one-sided P = 0.079]. One TelaE patient had a partial response and 26 had stable disease (SD). Eleven patients on PboE had SD. Treatment-emergent adverse events included fatigue, anemia, cough, dyspnea, elevated serum creatinine, and diarrhea; grade 3 to 4 events occurred in 74% TelaE patients versus 61% PboE. Conclusions: TelaE was well tolerated and improved PFS versus PboE in patients with mRCC previously treated with TKIs and checkpoint inhibitors.
Effect of Banded Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy on Diabetes Remission at 5 Years Among Patients With Obesity and Type 2 Diabetes: A Blinded Randomized Clinical Trial
Authors: Rinki Murphy, Lindsay D. Plank, Michael G. Clarke, Nicholas J. Evennett, James Tan, David D.W. Kim, Richard Cutfield, Michael W.C. Booth
Journal: Diabetes Care (2022)

OBJECTIVE To determine whether silastic ring laparoscopic Roux-en-Y gastric bypass (SR-LRYGB) or laparoscopic sleeve gastrectomy (LSG) produces superior diabetes remission at 5 years. RESEARCH DESIGN AND METHODS In a single-center, double-blind trial, 114 adults with type 2 diabetes and BMI 35–65 kg/m2 were randomly assigned to SR-LRYGB or LSG (1:1; stratified by age-group, BMI group, ethnicity, diabetes duration, and insulin therapy) using a web-based service. Diabetes and other metabolic medications were adjusted according to a prespecified protocol. The primary outcome was diabetes remission assessed at 5 years, defined by HbA1c &amp;lt;6% (42 mmol/mol) without glucose-lowering medications. Secondary outcomes included changes in weight, cardiometabolic risk factors, quality of life, and adverse events. RESULTS Diabetes remission after SR-LRYGB versus LSG occurred in 25 (47%) of 53 vs. 18 (33%) of 55 patients (adjusted odds ratios 4.5 [95% CI 1.6, 15.5; P = 0.009] and 4.2 [1.3, 13.4; P = 0.015] in the intention-to-treat analysis). Percent body weight loss was greater after SR-LRYGB than after LSG (absolute difference 10.7%; 95% CI 7.3, 14.0; P &amp;lt; 0.001). Improvements in cardiometabolic risk factors were similar, but HDL cholesterol increased more after SR-LRYGB. Early and late complications were similar in both groups. General health and physical functioning improved after both types of surgery, with greater improvement in physical functioning after SR-LRYGB. People of Māori or Pacific ethnicity (26%) had lower incidence of diabetes remission than those of New Zealand European or other ethnicities (2 of 25 vs. 41 of 83; P &amp;lt; 0.001). CONCLUSIONS SR-LRYGB provided superior diabetes remission and weight loss compared with LSG at 5 years, with similar low risks of complications.
Ampullary Neuroendocrine Neoplasms: Identification of Prognostic Factors in a Multicentric Series of 119 Cases
Authors: Alessandro Vanoli, Oneda Grami, Catherine Klersy, Anna Caterina Milanetto, Luca Albarello, Matteo Fassan, Claudio Luchini, Federica Grillo, Paola Spaggiari, Frediano Inzani, Silvia Uccella, Paola Parente, Gennaro Nappo, Paola Mattiolo, Massimo Milione, Andrea Pietrabissa, Lorenzo Cobianchi, Marco Schiavo Lena, Stefano Partelli, Antonio Di Sabatino, Christine Sempoux, Carlo Capella, Claudio Pasquali, Claudio Doglioni, Fausto Sessa, Aldo Scarpa, Guido Rindi, Marco Paulli, Alessandro Zerbi, Massimo Falconi, Enrico Solcia, Stefano La Rosa
Journal: Endocrine Pathology (2022)

Neuroendocrine neoplasms (NENs) of the major and minor ampulla are rare diseases with clinico-pathologic features distinct from non-ampullary-duodenal NENs. However, they have been often combined and the knowledge on prognostic factors specific to ampullary NENs (Amp-NENs) is limited. The aim of this study was to identify factors associated with metastatic potential and patient prognosis in Amp-NENs. We clinically and histologically investigated an international series of 119 Amp-NENs, comprising 93 ampullary neuroendocrine tumors (Amp-NETs) and 26 neuroendocrine carcinomas (Amp-NECs). Somatostatin-producing tubulo-acinar NET represented the predominant Amp-NET histologic subtype (58 cases, 62%, 12 associated with type 1 neurofibromatosis). Compared to Amp-NETs, Amp-NECs arose in significantly older patients and showed a larger tumor size, a more frequent small vessel invasion, a deeper level of invasion and a higher rate of distant metastasis, and, importantly, a tremendously worse disease-specific patient survival. In Amp-NETs, the WHO grade proved to be a strong predictor of disease-specific survival (hazard ratio: 12.61, p < 0.001 for G2 vs G1), as well as patient age at diagnosis > 60 years, small vessel invasion, pancreatic invasion, and distant metastasis at diagnosis. Although nodal metastatic disease was not associated with survival by itself, patients with > 3 metastatic lymph nodes showed a worse outcome in comparison with the remaining Amp-NET cases with lymphadenectomy. Tumor epicenter in the major ampulla, small vessel invasion, and tumor size > 16 mm were independent predictors of nodal metastases in Amp-NETs. In conclusion, we identified prognostic factors, which may eventually help guide treatment decisions in Amp-NENs.
An artificial intelligence difficulty scoring system for stone removal during ERCP: a prospective validation
Authors: Li Huang, Youming Xu, Jie Chen, Feng Liu, Deqing Wu, Wei Zhou, Lianlian Wu, Tingting Pang, Xu Huang, Kuo Zhang, Honggang Yu
Journal: Endoscopy (2022)

A computer-assisted (CAD) system was developed to assess, score, and classify the technical difficulty of common bile duct (CBD) stone removal during endoscopic retrograde cholangiopancreatography (ERCP). The efficacy of the CAD system was subsequently assessed through a multicenter, prospective, observational study.All patients who met the inclusion criteria were included. Based on cholangiogram images, the CAD system analyzed the level of difficulty of stone removal and classified it into "difficult" and "easy" groups. Subsequently, differences in clinical endpoints, including attempts at stone extraction, stone extraction time, total operation time, and stone clearance rates were compared between the two groups.173 patients with CBD stones from three hospitals were included in the study. The group classified as difficult by CAD had more extraction attempts (7.20 vs. 4.20, P < 0.001), more frequent machine lithotripsy (30.4 % vs. 7.1 %, P < 0.001), longer stone extraction time (16.59 vs. 7.69 minutes, P < 0.001), lower single-session stone clearance rate (73.9 % vs. 94.5 %, P < 0.001), and lower total stone clearance rate (89.1 % vs. 97.6 %, P = 0.019) compared with the group classified as easy by CAD.The CAD system effectively assessed and classified the degree of technical difficulty in endoscopic stone extraction during ERCP. In addition, it automatically provided a quantitative evaluation of CBD and stones, which in turn could help endoscopists to apply suitable procedures and interventional methods to minimize the possible risks associated with endoscopic stone removal.